The present invention relates to a device for feeding a powder in a predetermined amount and a method thereof. As a typical example, the present invention relates to a multi-dose powdered medicine administering device.
More specifically, the invention relates to a powdered medicine multi-dose administering device by which a powdered medicine of an amount of plural times of administration operations stored in the-device body is extracted and weighed into a unit dose of powdered medicine of a constant quantity, which is a very small amount, and is sprayed.
The invention further provides a relatively inexpensively constructed multi-dose powdered medicine administering device by which a unit dose of powdered medicine can be consecutively and precisely extracted and administered into the body cavity such as the nasal cavity, oral cavity, trachea, bronchus or lung, or into any other diseased part by spraying or inhalation, the device being sanitary, suited to being carried and easy to use.
Powdered medicine can be administered into a body cavity such as the nasal cavity, oral cavity or airway by means of spraying or inhalation. For example, the powdered medicine is administered by spraying into the nasal cavity of a patient suffering from a nasal allergy, or is administered by inhalation into the air ways of a patient suffering from asthma. For a patient suffering from stomatitis, the powdered medicine is administered by spraying into the oral cavity. Recently, attention has been given to a drug delivery system in which a medicine is absorbed into the bloodstream through the mucous membrane of the nasal cavity or lung, and it has been attempted to administer powdered medicine via a mucous membrane. Peptide/proteinous drugs such as insulin and calcitonin, as well as drugs which must exhibit immediate effect such as migraine-relieving drug and the like drugs have been produced in the form of powdery orally administering agents or inhalable agents that can be conveniently used as substitutes for injected drugs, and it has been frequently reported that such drugs are more favorably absorbed than the orally administered drugs.
To administer the powdered medicine, a powdered medicine administering device is used. Powdered medicine administering devices are roughly classified into one of the two types according to the system for storing the powdered medicine.
In the first type of powdered medicine administering device, a powdered medicine in an amount of a unit-dose administering operation is accommodated in the administering device or in an appropriate container such as a capsule. Therefore, a unit-dose of powdered medicine is administered at each administering operation. This includes those of the disposable type that are discarded after each administering operation.
In the second type of powdered medicine administering devices, a powdered medicine in an amount of many times-of administering operations is accommodated in an appropriate container. Each time an administering operation is carried out, an accurate unit-dose of powdered medicine is extracted from the container and is administered.
In the present invention, the amount of powdered medicine to be administered in a single operation is defined as a xe2x80x9cunit-dosexe2x80x9d, and the amount of powdered medicine to be administered in a plurality of operations. is defined as a xe2x80x9cmulti-dosexe2x80x9d.
As an example of the powdered medicine unit-dose administering device, Japanese Unexamined Patent Publication (Kokai) No. 59-34267 discloses one which sprays the powdered medicine into the nasal cavity. In these administering devices, in general, a unit-dose of the powdered medicine is contained in a container such as a capsule, and provision is made of means for piercing the container and air stream introduction means for spraying the powdered medicine from the container into the nasal cavity of a patient. As an example of the disposable unit-dose administering device, International Patent Publication No. 2-500172 discloses an administering device which contains a fine powdery medicine, and includes a holding unit forming an opening in the head portion thereof for spraying the medicine so as to be inhaled, and air introduction means, the bottom of the holding unit being communicated with the air introduction means through an air-permeable diaphragm which does not permit the passage of the medicine. Further, WO 97/04826. discloses an administering device which is an improvement on the above device.
Concerning the unit-dose inhaler by which powdered medicine is inhaled into the air ways, a large number of devices have been proposed. For example, there is provided an inhaler employing capsules that are usually used pharmacologically. In each capsule, a unit-dose of powdered medicine is accommodated. Each administering device is provided with means for piercing the capsule. After the capsule is pierced, the powdered medicine is administered by the air flow created by the inhaling action of the user. The administering devices have their features in the air flow at the time of inhaling and in the state of the capsule. U.S. Pat. Nos. 3,906,950 and 4,013,075 disclose devices in which both ends of the capsule are pierced and the capsule remains stationary during the inhalation, and U.S. Pat. No. 3,807,400 discloses the one in which the capsule moves during the inhalation.
As an example of a multi-dose administering device, the specification of WO 94/26338 (corresponding to U.S. Pat. No. 5,634,900xe2x80x94Makino et al.) discloses one which administers the medicine by spraying. This specification discloses a device comprising a storage chamber detachably attached to the device body and storing multi-dose of medicine, a container chamber having a unit dose capacity, medicine distribution means movably attached to the device body and communicated at the filling position with the storage chamber and with the container chamber to administer the medicine in the container chamber, and pumping means communicated at the filling position with the container chamber to inject air into the storage chamber to stir up the medicine in the storage chamber, wherein the container chamber is filled with a predetermined amount of powdered medicine after stirring as it is transferred from the storage chamber by the sucking force created by the pumping means or by gravity.
As a nasal cavity administering device, European Patent Publication No. 0744188 discloses a nasal cavity applicator comprising a manual air-flow supply source for spraying powdered medicine, a storage chamber for storing multi-dose of powdered medicine, a pipe for passing the powdered medicine, and means for distributing the multi-dose of powdered medicine into a unit doses of powdered medicine. Means for distributing the powdered medicine includes a drum-shaped powdered medicine storage chamber and a rotary sleeve having, on the inside thereof, a plurality of container chambers for containing a unit doses of medicine.
As a device for administering powdered medicine into the air ways by inhalation, European Patent Publication No. 0211595 discloses a device in which a disk-shaped pack is loaded into the device, and a series of bubbles are arranged around the pack under the condition that the distances from the bubbles to the center of the pack are the same. A predetermined quantity (unit-dose) of powdered medicine is accommodated in each bubble. This pack is put on the rotary circular tray about the center axis. The tray has holes at positions corresponding to the bubbles, and when each bubble is moved to a position where it is broken by an appropriate opening device, powdered medicine is taken out from the bubble and is inhaled.
Further, European Patent Publication No. 0069715 discloses the following device. This administering device includes a container, accommodating a predetermined quantity of medicine, and a device for taking out powdered medicine accommodated in the container so as to prepare for the administration of the medicine. The administration preparation device is composed of a plate having a predetermined thickness and a predetermined number of through-holes. The plate is capable of moving from a position at which the through-holes are partly filled with powdered medicine taken out from the container by a mechanical means, to a position at which the holes filled with the medicine are located in the passage. When the user inhales through an inhalation port communicated with the passage, the air enters into the passage, so that the powdered medicine can be taken out from the through-hole. There is provided a scraper, which scrapes the powdered medicine on the container side in the through-hole formed in the plate. According to this specification, the through-holes are completely filled by the action of the scraper. Therefore, a constant dose can be ensured. According to this specification, it is described that the scraper is optionally provided. However, in order to appropriately operate the inhaler, it is necessary to provide the scraper because the doses differ greatly without the scraper. This is because the powdered medicine in many cases has poor fluidity and it frequently occurs that the through-holes are not completely filled with the powdered medicine.
Though many administering devices have heretofore been contrived, they have their problems as described above.
When a unit-dose administering device is compared with a multi-dose administering device, the multi-dose administering device is preferred from the viewpoint of convenience and marketability. This is because, in the case of the unit-dose administering device as disclosed in, for example, Japanese Unexamined Patent Publication (Kokai) No. 59-34267, a container such as capsule is necessary to contain a unit-dose of medicine and, besides, the device must be equipped with means for piercing the container. Therefore, the user must mount the container containing the powdered medicine and must pierce it according to the instruction of the administering device. This is never convenient for the user. The user must carry with him the administering device as well as the container containing the powdered medicine, which is not convenient, either. The specification of WO 97/04826 discloses a device which requires a simplified administering operation. In this case, however, the user who needs a plurality of times of administration must use an administering device containing a plural number of unit-dose medicines, accompanied by a problem from the viewpoint of portability.
The multi-dose administering device is free from the defect related to convenience inherent in the unit-dose administering device but is accompanied by another important problem. That is, it is very difficult to consecutively and quantitatively extract and administer the powdered medicine in an amount necessary for a unit-dose of administration from a large amount of the powdered medicine in a collected form, due to changes in the density of the collected powdered medicine.
Several contrivances have been made to solve the above-mentioned problem. For example, European Patent Publication No. 0069715 mentioned above discloses a method-of continuously filling through-holes of a predetermined capacity with the powdery medicine while holding the hole with a scraper or the like. Even with this method, however, the bulk density of the powdered medicine changes when the administering device as a whole is vibrated, whereby the through-holes of the predetermined amount are filled with varying amounts of the medicine; i.e., the medicine is not administered in a constant amount to the living body. European Patent Publication No. 0744188 discloses means for quantitatively dividing the medicine, i.e., discloses a rotary sleeve equipped with a drum-shaped powdered medicine storage chamber and a container chamber formed on the inside thereof for containing plural unit-dosage medicines. However, the device is relatively complex, uses a large number of parts which are difficult to mold and, hence, is expensive.
Japanese Unexamined Patent Publication (Kokai) No. 3-18376 discloses a multi-dose administering device in which a large quantity of powdered medicine is compressed, and the compressed body of powdered medicine is continuously and quantitatively divided and peeled into pieces. According to this method, the powdered medicine is compressed to ensure a predetermined quantity of the divided medicine. Even with this method, however, when the administering device is vibrated, the bulk density of the compressed powdered medicine changes, resulting in a change in the weight of the compressed powdered medicine that is peeled off. Therefore, the medicine is not administered in a constant amount to the living body. Further, means for uniformly dividing the powdered medicine is relatively complex. To put it into clinical use, therefore, problems are involved such as difficulty in the molding and cost of production.
The specification of WO 94/96338 teaches a multi-dose administering device in which the air- flow passes into the powdered medicine collected in the storage chamber just prior to the dividing operation, the. medicine in the collected form is moved in space in the storage chamber to prevent a change in the density of the powdered medicine and the powdered medicine of an amount of a unit-dose is contained in the powdered medicine container chamber, due to the sucking force and/or gravity, so that the unit-dose of medicine is continuously and quantitatively administered after being divided. However, this device includes a storage unit, a medicine container chamber for containing medicine of a unit-dose, a medicine-metering means and a pumping means and, further, requires a sufficient space for moving the powdered medicine without causing a change in the density. Thus, as the device needs complex parts and is bulky, it is not suited for being carried.
It is desired that the powdered medicine is dispersed into primary particles at a moment when the medicine separates away from the administering device and settles on the administered portion. However, it has been known that the particles cohere during the preservation to form secondary particles; i.e., the particle size distribution shifts toward the larger side. It is therefore desired that even if the powdered medicine is cohered in the administering device during the storage, the powdered medicine is dispersed again into the primary particles at the time when it leaves the administering device.
In a system in which the medicine is divided, in a predetermined volume, into a unit dose in the medicine-containing chamber, the weight of the divided medicine undergoes a change when the bulk density of the powdered medicine changes depending upon the lot number of the medicine. It is therefore desired to adjust the volume of the medicine that is administered depending upon a change in the bulk-density of the medicine.
As described above, none of the conventional powdered medicine administering devices satisfy the requirements of metering the medicine to be administered, providing portability by decreasing the size, easy operability, quick operability, easy production steps, simple constituent parts, low cost of production, and a good dispersing property of the powdered medicine particles.
In view of the above-mentioned problems and assignments of the prior art, the present invention provides a powdered medicine multi-dose administering device that is described below.
That is, the object of the present invention is to provide a powdered medicine multi-dose administering device which satisfies the requirements of spraying the medicine in a predetermined amount, having a small size (portability), an easy and quick operation, an easy production steps, a dispersion of the powdered medicine and a decreased number of parts and low cost.
That is, the present invention is concerned with a powdered medicine multi-dose administering device comprising: means for defining a medicine storage chamber capable of storing a multi-dose amount of powdered medicine; a medicine container unit provided under the bottom surface of said medicine storage chamber and is capable of containing a single-dose amount of powdered medicine; a medicine guiding unit capable of moving between a filling position and an administering position while remaining in contact with the bottom surface of said medicine storage chamber, and, when moved to the filling position, causes said medicine container unit to be opened to said medicine storage chamber through opening means and, when moved to the administering position, causes said medicine container unit to be closed with respect to said medicine storage chamber and causes said medicine container unit to be communicated with the exterior of the device through a pipe; means operated from the outer side of the device to move said medicine guiding unit between the filling position and the administering position; and a pump unit capable of blowing the air into said medicine container unit through a filter provided in the bottom of said medicine container unit; wherein said medicine guiding unit, at the filling position, enables said medicine container unit to be filled with the powdered medicine from said medicine storage chamber through said opening means, sweeps and meters the powdery medicine in said medicine container unit into the amount of one time of administering operation as it moves from the filling position to the administering position, and, at the administering position, permits the powdery medicine in said medicine container unit to be injected out of the device, together with the air, through said pipe when said pump unit is operated.
According to the present invention, the medicine guiding unit can be easily moved upon being operated from the outer side of the device. When the medicine guiding unit is at the filling position, the powdered medicine in the powdered medicine storage chamber falls into the medicine container unit through opening means provided in the medicine guiding unit, and is filled therein. When the medicine guiding unit moves from the filling position to the administering position, the powdered medicine in the medicine container unit is swept and is metered into the amount of one time of administering operation corresponding to the content of the medicine container portion. Thereafter, the medicine container portion is closed. When the medicine guiding portion further moves to arrive at the administering position, the opening of the pipe of the medicine guiding unit comes into match with the medicine container unit. Upon operating the pump unit, therefore, the air is blown into the medicine container unit, and the powdered medicine in the medicine container unit is ejected, together with the air, out of the device through the pipe.
The medicine storage chamber and the medicine container portion are molded integrally together by using a resin to define a body of the device. This makes it possible to simplify the structure of the device body including the medicine storage chamber and the medicine container unit, and to easily produce the device body.
The medicine guiding unit includes a lower disk-like portion and a pole-like portion extending upward from the disk-like portion, which are integrally molded together using a resin, the opening means is so formed as to penetrate vertically through the disk-like portion, and the pipe is opened at its one end on the lower surface of the disk-like portion and is opened at its other end in the upper end of the pole-like portion. The medicine guiding unit is molded as a unitary structure using a resin. Therefore, the opening means and the pipe work to fill and administer the powdered medicine.
The device body is nearly of a cylindrical shape, the disk-like portion of the medicine guiding unit has a diameter smaller than the inner diameter of the medicine storage chamber of the device body, and the medicine guiding unit is allowed to rotate between the filling position and the administering position over a predetermined angular range. Therefore, the medicine guiding unit can be changed over between the filling position and the administering position relying simply upon the rotary operation.
The device body has a closure unit on the medicine storage unit, the closure unit has a shaft hole at the center thereof for passing through the pole-like portion of the medicine guiding unit, and the medicine storage chamber is sealed with the closure unit, medicine storage unit and medicine guiding unit. Thus, the sealing of the medicine storage chamber is maintained, preventing undesired leakage of the powdered medicine.
The bottom surface of the disk-like portion of the medicine guiding unit comes in contact with the bottom surface of the medicine storage chamber, the upper and lower positions of the medicine guiding unit are limited by a contact portion formed on the pole-like portion so as to come into contact with the closure unit, and the bottom surface of the disk-like portion of the medicine guiding unit is brought into intimate contact with the bottom surface of the medicine storage chamber. This maintains an intimate contact between the bottom surface of the disk-like portion of the medicine guiding unit and the bottom surface of the medicine storage chamber, to guarantee correct metering of the powdered medicine and reliable operation.
The medicine guiding unit has a shaft of a circular shape in cross section formed in the upper part of the junction portion of the pole-like portion so as to be fitted to the shaft hole of the closure unit, and has a shaft of a non-circular shape in cross section formed in the upper part thereof, the means operated from the outer side of the device to move the medicine guiding unit between the filling position and the administering position, is a rotary spray metering change-over device which has a non-circular hole that fits to the shaft of a non-circular shape in cross section of the pole portion of the medicine guiding unit, and the medicine guiding unit moves between the filling position and the administering position being interlocked to the rotational operation of the change-over device. By simply rotating the rotary spray metering change-over device from the outside of the device, therefore, the medicine guiding unit can be changed over between the filling position and the administering position, facilitating the operation.
The rotary spray metering change-over device includes a cylindrical portion having a large diameter and a cylindrical portion having a small diameter, that are molded integrally together using a resin, the outer periphery of the cylindrical portion having a large diameter forms a rotary operation portion, and the cylindrical portion of a small diameter defines a powdered medicine passage formed therein, has the non-circular hole formed in the base portion, and defines a spray port in an end thereof. The change-over operation is easily effected by using the cylindrical portion having a large diameter of the change-over device, and the cylindrical portion of a small diameter forms a portion of the powdered medicine passage. Accordingly, the powdered medicine is conveyed up to the spraying port at an end of the device, and is sprayed onto the diseased part.
The rotary spray metering change-over device is formed to be detachable from the device body 1 and the medicine guiding unit. Thus, the change-over device can be removed from the device body and from the medicine guiding unit can be removed from the administering device itself, can be washed and can be easily re-attached to the administering device.
A central hole is formed at the center in the bottom surface of the disk-like portion of the medicine guiding unit, and a protuberance is formed at the center on the bottom surface of the medicine storage chamber to work as a shaft that fits to the central hole in order to stabilize the turning of the medicine guiding unit. Accordingly, the turning of the medicine guiding unit is stabilized, and the rotary spray metering change-over device can be easily turned.
The medicine guiding unit has an arcuate groove formed in the bottom surface of the disk-like portion with the central hole as a center, the medicine storage unit has a protuberance formed on the bottom surface thereof so as to be inserted in the arcuate groove thereby to limit the turning range of the medicine guiding unit and of the rotary spray metering change-over device, wherein, when the protuberance is located at an end of the arcuate groove, the position for filling the powdered medicine is limited and, when the protuberance is located at the other end, the position for administering the powdered medicine is limited.
On the bottom surface of the disk-like portion of the medicine guiding unit, an angle (x) subtended by the center of the opening means and the center of the opening of the pipe is equal to, or is slightly smaller than an angle (y) subtended by one end and other end of the arcuate groove (xxe2x89xa6y), and lies over a range of from 60 degrees to 180 degrees.
The disk-like portion of the medicine guiding unit on the side of the medicine storage chamber is inclined upward from the periphery toward the center at an angle (xcex1) in a range of from 15 degrees to 45 degrees with respect to the bottom surface of the disk-like portion.
The pipe provided in the medicine guiding unit is inclined upward at angles (xcex2, xcex3) in a range of from 20 degrees to 70 degrees with respect to the bottom surface of the medicine guiding unit. The powdered medicine smoothly flows through the pipe at the time when the powdered medicine in the medicine container chamber is injected by operating the pump unit.
The opening means in the medicine guiding unit is a hole penetrating vertically through the disk-like portion.
The hole extends upward from the opening in the bottom surface of the disk-like portion, and expands on the side facing the medicine storage chamber toward the side of the opening of the pipe thereby to form a pocket-like dent, the dent assisting a smooth conveyance of the powdered medicine in the medicine storage chamber into the medicine container chamber during the operation for changing over the filling and administering.
Here, regarding the size of the dent, the medicine can be smoothly conveyed into the medicine container chamber during the operation of the rotary spray metering change-over device when the area of the dent facing the side of the medicine storage chamber is in a range of from 0.1 times to 2.5 times of the opening area and, particularly, from 0.5 times to 1 times of the area of the hole facing the bottom surface of the disk-like portion. As for the depth of the dent, there is no limitation on the depth provided the diameter of the hole remains unchanged on the side of the medicine container chamber. In practice, due to the difficulty in the molding, the depth of the dent is from 10 to 80% and, particularly preferably, 50% of the depth of the hole.
The dent also decreases the thickness of the disk-like portion of the medicine guiding unit. Reduction in the thickness contributes to preventing the contraction or expansion caused by the heat in the medicine guiding unit during the molding, and makesit possible torealize a highly precise spraying performance which is a feature of the powdered medicine multi-dose administering device.
One or plural pieces of vanes are formed on the outer side of the pole-like portion of the medicine guiding unit, so that the powdered medicine in the medicine storage chamber is stirred as the medicine guiding unit moves between the filling position and the administering position.
Here, the vanes possessed by the medicine guiding unit are molded as singe part using the same material as the medicine guiding unit, and may have any shape or thickness provided they can be molded as a single part as described above. The angle subtended by the vanes and the center line of the medicine passage in the guiding unit may lie over a range of from parallel relation, i.e., from 0 degree to 90 degrees but desirably liles in a range of from 0 degree to 45 degrees from the viewpoint of accomplishing a high stirring efficiency of the medicine in the medicine storage chamber during the rotary operation of the,change-over device. When the vanes are provided, it is better that the number of the vanes is two than the number of the vanes is one, since the medicine is more efficiently stirred in the medicine storage chamber due to the rotational operation of the change-over device.
The pump unit is at least partly constituted by a flexible resin so as to define an air chamber therein, the opening portion of the pump unit is coupled to the lower part of the device body, the pump unit is depressed and relaxed to blow the air into the medicine container chamber through the filter in the air chamber, and the powdered medicine is blown out of the device through the pipe.
The filter has a recessed portion or a protruded portion on the side facing the medicine container chamber to adjust the volume of the medicine container chamber. In this case, the size of the recessed portion or of the protruded portion of the filter is changed, and the direction .of the filter is changed, to freely change the volume of the medicine container chamber and to adjust the amount of the powdered medicine administered in one time of administering operation.
The medicine guiding unit is obtained by molding one or more kinds of high-molecular materials selected from the group consisting of a polycarbonate, ABS, a high-impact polystyrene and a cyclic olefin copolymer.
Further, a drying agent is mounted on a portion of the device, the powdered medicine administering device is obtained in a disposable type, and it is realized for administration into the body cavity, into the nasal cavity or into the lung.
FIG. 1 is a sectional view illustrating a powdered medicine multi-dose administering device according to an embodiment of the present invention;
FIG. 2 is a sectional view illustrating a medicine storage unit (5) in a device body (1);
FIG. 3 is a sectional view illustrating a closure unit (4) in the device body (1);
FIG. 4 is a sectional view illustrating a whole medicine guiding unit (2);
FIG. 5 is a view illustrating the bottom of the medicine guiding unit (2);
FIG. 6 is a sectional view illustrating a rotary spray metering change-over device (13);
FIG. 7 is a sectional view illustrating a pump unit (3);
FIG. 8 is a sectional view illustrating a device cover (9);
FIG. 9 is a sectional view illustrating a medicine container chamber (5b) inclusive of a filter (6) provided with a cylindrical protuberance;
FIG. 10 is a perspective view illustrating an example of the filter (6) provided with a cylindrical protuberance;
FIG. 11 is a view illustrating near the bottom surface of the medicine guiding unit (2) and shows an angle of a pipe (2g);
FIG. 12 is a view illustrating near the bottom surface of the medicine guiding unit (2) and where the direction of the pipe (2g) is changed; and
FIG. 13 is a view illustrating near the bottom surface of the medicine guiding unit (2) and where the direction of the pipe (2g) is changed